Protective Role of Somatostatin in Sepsis-Induced Intestinal Barrier Dysfunction through Inhibiting the Activation of NF-κB Pathway

Abstract EN

Somatostatin (SST) has a protective role in intestinal injury, inflammatory response, and intestinal mucosal barrier in rats with acute pancreatitis.

However, its function in sepsis-induced intestinal barrier dysfunction remains largely unknown.

A mouse sepsis model was constructed, and SST was injected into the tail vein.

Then, hematoxylin and eosin staining (HE) was used to detect the intestinal barrier dysfunction.

Enzyme-linked immunosorbent assay was used to detect the level of tumor necrosis factor α- (TNF-) α, interleukin- (IL-) 6, and interleukin- (IL-) 10 in the ileum.

Expressions of tight junction proteins, zonula occludens- (ZO-) 1 and Claudin-1, and NF-κB p65 in the ileum were detected using western blot and immunohistochemistry as needed.

Furthermore, JSH-23 as an inhibitor of the NF-κB pathway was injected into sepsis mice with SST or not.

Mice with sepsis showed an obvious intestinal barrier dysfunction with decreasing specific somatostatin receptor subtype (SSTRs), and increasing TNF-α, IL-6, and IL-10 in the ileum.

SST could relieve the injury, the decrease of SSTRs, and the increase of TNF-α and IL-6 induced by sepsis and also further enhanced the expression of IL-10.

Further analysis showed that ZO-1 and Claudin-1 were reduced in the ileum by sepsis but enhanced by SST.

NF-κB p65 was promoted in the ileum by sepsis but inhibited by SST.

Further experiments confirmed that NF-κB inhibitor JSH-23 could repair the intestinal barrier dysfunction and enhance the protective effect of SST on the intestinal barrier.

SST, with a protective effect on intestinal barrier dysfunction through suppression of NF-κB, could be a potential therapeutic drug for sepsis-induced intestinal barrier dysfunction.